Total Tumor Volume Is a Better Marker of Tumor Burden in Hepatocellular Carcinoma Defined by the Milan Criteria

Background

The Milan criteria are used to define small hepatocellular carcinoma (HCC) and to select patients for curative treatments. Total tumor volume (TTV) is an alternative parameter for tumor burden. We aimed to evaluate whether TTV is a feasible prognostic marker in HCC patients with upper boundary TTV of 65.5 cm³, which is equivalent to a single 5 cm tumor nodule defined by the Milan criteria.

Methods

A total of 774 HCC patients with TTV <65.5 cm³ receiving surgical resection, liver transplantation, or radiofrequency ablation (RFA) as the primary treatment were retrospectively analyzed.

Results

Of these patients, 50 (6.5 %) did not fulfill the Milan criteria. Patients beyond the Milan criteria more often had larger tumor size and TTV, as well as more tumor nodules (p values all <0.01). There was no significant survival difference between patients within and beyond the Milan criteria (p = 0.205). Patients with TTV >15 cm³ had a significantly poorer survival than patients with TTV <15 cm³ (p = 0.007). There was no survival difference between patients receiving surgical treatments versus RFA (p = 0.932). In the Cox proportional hazards model, TTV >15 cm³ [risk ratio (RR): 1.474, p = 0.005], serum bilirubin ≥1.5 mg/dL (RR: 1.663, p = 0.003), serum sodium <135 mmol/L (RR: 2.016, p = 0.01), and α-fetoprotein (AFP) ≥100 ng/mL (RR: 1.37, p = 0.033) were independent predictors of poor prognosis.

Conclusions

Total tumor volume, is an independent and better prognostic marker than the Milan criteria to indicate tumor burden in HCC patients who had tumor volume defined by the Milan criteria and underwent curative therapies.     

Milan Criteria, Multi-nodularity, and Microvascular Invasion Predict the Recurrence Patterns of Hepatocellular Carcinoma After Resection

Aims

This study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated.

Methods

A total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis.

Results

After a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p?=?0.011; low vs. high, p?<?0.001; medium vs. high, p?=?0.009).

Conclusions

The combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.     

Survival Advantage of Radiofrequency Ablation Over Transarterial Chemoembolization for Patients with Hepatocellular Carcinoma and Good Performance Status Within the Milan Criteria

Background

Performance status is closely linked with survival in patients with hepatocellular carcinoma (HCC). We evaluated the impact of performance status on patients with small HCC receiving radiofrequency ablation (RFA) versus transarterial chemoembolization (TACE).

Methods

A total of 424 and 282 patients within the Milan criteria undergoing RFA and TACE, respectively, were analyzed. Patients were classified as performance status 0 (n = 516) and performance status ≥1 (n = 190) groups. A propensity-score matching analysis with preset caliper width was used. A total of 167 and 68 matched pairs were selected from patients with a performance status of 0 and ≥1, respectively.

Results

Radiofrequency ablation provided significantly better long-term survival than TACE for patients within the Milan criteria (p < 0.01). After being stratified by performance status and matched in the propensity model, the baseline characteristics were similar between the RFA and TACE groups for patients with a performance status of 0 or ≥1. RFA provided significantly better long-term survival than TACE in patients with a performance status of 0 in the propensity model (p < 0.05); TACE was significantly associated with 1.784-fold increased risk of mortality (95 % confidence interval 1.075–2.506) by using the Cox proportional hazards model. TACE was not a significant prognostic predictor in patients with a performance status ≥1 in the propensity model.

Conclusions

For HCC patients within the Milan criteria with a performance status of 0, RFA provides better long-term survival than TACE. RFA should be considered a priority treatment in inoperable HCC patients within the Milan criteria. Performance status is a feasible surrogate marker to enhance treatment allocation.     

Surgical Resection Is Better than Transarterial Chemoembolization for Hepatocellular Carcinoma Beyond Milan Criteria Independent of Performance Status

Background and Aims

Performance status is tightly linked with survival in patients with hepatocellular carcinoma (HCC). We investigated the impact of performance status on HCC patients beyond the Milan criteria receiving surgical resection (SR) or transarterial chemoembolization (TACE).

Methods

A total of 909 patients with HCC beyond the Milan criteria were retrospectively analyzed by using propensity score analysis.

Results

The baseline characteristics were similar between the SR and TACE group for patients with performance status 0 in the propensity model. More patients in the TACE group with performance status ≥1 had Child-Turcotte-Pugh class A compared to the SR group (p?=?0.044) in the propensity model. SR provided significantly better long-term overall survival than TACE in patients selected in the propensity model regardless of performance status (both p?TACE was associated with 2.279-fold and 3.066-fold increased risk of mortality in performance status 0 and performance status ≥1 in the propensity model (95 % confidence interval, 1.476–3.591 and 1.570–5.989), respectively.

Conclusions

For either performance status 0 or ≥1 HCC patients beyond the Milan criteria, SR provides significantly better long-term survival than TACE. SR should be considered a priority treatment in these patients independent of performance status.     

Intraoperative Ablation for Small HCC not Amenable for Percutaneous Radiofrequency Ablation in Child A Cirrhotic Patients

Background

Radiofrequency ablation (RFA) was initially started by radiologists as a percutaneous treatment, but surgeons started to use RFA by surgical approach for patients with tumors at locations difficult for the percutaneous procedure. The aim was to evaluate the results of intraoperative RFA for small hepatocellular carcinomas (HCCs) (<3 cm) in locations difficult for a percutaneous approach.

Methods

Two hundred forty-seven patients with small solitary HCC (<3 cm) were treated; 196 via percutaneous RFA while 51 patients presented at sites not amenable for percutaneous route. Twenty-seven out of 51 patients underwent surgical resection, while 24/51 patients underwent intraoperative RFA.

Results

The location and depth of the tumor from the liver capsule was the only significant factors in the choice of the surgeon between resection and RFA. RFA was successful in all tumors (complete ablation rate of 100 %). In the surgery group, all patients achieved R0 resection. Complication rate was comparable (p?=?1.0). After a median follow-up of 37 months (range, 10–45 months), no tumors showed neither local progression nor local recurrence and no significant difference was observed between two groups as regards early recurrence and number of de novo lesions (p?=?0.49). One-year and 3-year survival rates were 93 % and 81 %, respectively, in the resection group comparable to the corresponding rates of 92 % and 74 % in the RFA group (p?=?0.9).

Conclusion

For small HCC in locations difficult for a percutaneous approach, intraoperative RFA can be an alternative option for deep-seated tumors necessitating more than one segmentectomy achieving similar tumor control, and overall and disease-free survival.     

γ-Glutamyltranspeptidase is a Prognostic Marker of Survival and Recurrence in Radiofrequency-Ablation Treatment of Hepatocellular Carcinoma

Purpose

Serum γ-glutamyltranspeptidase (GGT) level, which is often elevated in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress marker which correlates with inflammation in the extracellular hepatic microenvironment. The aim of this study was to investigate the prognostic significance of GGT serum levels in patients undergoing radiofrequency ablation (RFA) therapy for the treatment of HCC.

Methods

This retrospective study included 254 patients with small liver cancer (tumor of ≤5 cm in diameter and nodule of ≤3 cm) who had been treated with RFA. Baseline serum GGT was examined before therapy, and overall survival (OS) and recurrence-free survival were evaluated by the Kaplan–Meier method. Univariate and multivariate analyses were used to analyze the significance of GGT and other serum markers as prognostic factors.

Results

After a median follow-up of 27 months, 51 patients had died and 123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003), GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk factors for recurrence.

Conclusions

Serum GGT is a convenient prognostic biomarker related to OS and recurrence in HCC patients undergoing RFA treatment.     

Surgical Resection in Hepatocellular Carcinoma Patients with Minimal Background Fibrosis: A Strategy in the Era of Organ Shortage

Background

Surgical therapies for hepatocellular carcinoma (HCC) represent the potentially curative approaches and provide patients the greatest survival advantage. We sought to examine the outcomes of patients with HCC treated with surgical resection, transplantation, and local ablation.

Methods

The Surveillance, Epidemiology, and End Results database was queried for all patients with nonmetastatic HCC from 2004 to 2007 who underwent local ablation (LA), segmental resection (SR), hemihepatectomy or extended resection (ER), or transplantation (TP).

Results

Of 16,209 patients with HCC, 3,989 (24.6 %) met criteria for inclusion and received therapies: 1,550 LA (39 %), 703 SR (18 %), 619 ER (16 %), and 1,117 TP (28 %). AFP was elevated in 69 % (2,026 of 2,921), and fibrosis grade 0–4 was noted in 32 % (368 of 1,156). The 3-year survival by procedure was 34 % (LA), 50 % (SR), 54 % (ER), and 74 % (TP), p = .001. In patients with minimal fibrosis, 1-year survival for patients undergoing resection was similar to TP (85 vs. 92 %, p = .346), but greater than LA (69 %, p = .001).

Discussion

Survival after surgical resection for HCC patients without extensive fibrosis appears to be superior to ablation and non-inferior to transplantation. In an era of organ shortage, transplantation may be better reserved for patients with cirrhosis and/or unresectable disease.     

Medium-Sized (3.1–5.0 cm) Hepatocellular Carcinoma: Transarterial Chemoembolization Plus Radiofrequency Ablation Versus Radiofrequency Ablation Alone

Purpose

This study was designed to retrospectively compare the effectiveness of combined transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with that of RFA alone in patients with medium-sized (3.1–5.0 cm) hepatocellular carcinoma (HCC).

Methods

From March 2000 to April 2010, 57 patients, each with a single medium-sized HCC, were treated with combined TACE and RFA, and 66 were treated with RFA alone.

Results

During follow-up (mean, 42.5 ± 33.2 months; range, 2.6–126.2 months), local tumor progression was observed in 40% of treated lesions in the combined treatment group and in 70% in the RFA-alone group. The 1-, 3-, 5-, and 7-year local tumor progression rates were significantly lower in the TACE + RFA group (9%, 40%, 55%, and 66%, respectively) than in the RFA-alone group (45%, 76%, 86%, and 89%, respectively; P < 0.001). Multivariate analysis showed that treatment allocation (odds ratio [OR], 1.78; P = 0.016) and Child-Pugh class (OR, 1.96; P = 0.008) were significant independent factors associated with patient survival. The rates of major complications were 0% for the combined treatment group and 3% for the RFA-alone group.

Conclusions

The combination of TACE and RFA is safe and provides better local tumor control than RFA alone for the treatment of patients with medium-sized HCC. Our multivariate analysis showed that RFA-alone treatment and Child-Pugh class B were poor independent factors for determining the patient survival period.     

Surgical Resection Versus Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Propensity Score Analysis

Background

The long-term survival in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) who received surgical resection (SR) or transarterial chemoembolization (TACE) remains unclear. We compared the efficacy of SR and TACE by using a propensity score analysis.

Methods

A total of 247 and 181 HCC patients with PVTT undergoing SR and TACE, respectively, were evaluated. One hundred eight pairs of matched patients were selected from each treatment arm by using a propensity score analysis.

Results

Of all patients, the estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 85 versus 60 %, 68 versus 42 %, and 61 versus 33 %, respectively (p < 0.001). Patients selected for SR were significantly younger and had better liver functional reserve, performance status, and smaller tumor burden. In the propensity model, the survival benefit of SR remained significant. The estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 84 versus 71 %, 69 versus 50 %, and 59 versus 35 %, respectively (p = 0.004). The two groups of patients in the propensity score analysis were similar in baseline characteristics. In the Cox proportional hazards model, patients receiving TACE had a 2.044-fold increased risk of mortality compared with patients receiving SR (95 % confidence interval: 1.284–3.252, p = 0.003).

Conclusions

For either unselected patients or patients in the propensity model, SR provides significantly better long-term survival than TACE. SR should be considered as a priority treatment in this subgroup of HCC patients.     

Microvascular Infiltration has Limited Clinical Value for Treatment and Prognosis in Hepatocellular Carcinoma

Background

Microvascular infiltration (MVI) is considered a necessary step in the metastatic evolution of hepatocellular carcinoma (HCC), but its prognostic value after liver resection (LR) is uncertain. We studied the clinical value of MVI compared to the Milan criteria in a consecutive series of patients submitted to radical LR.

Methods

A total of 441 patients were retrospectively evaluated. MVI and the Milan criteria were analyzed and compared as prognostic factors for overall and disease-free survival (DFS).

Results

MVI was present in 189 patients (42.8 %). Grading, satellitosis, size of cancer, and alfa fetoprotein value were significantly related to MVI, which was present in 34.3 and 53.2 % of Milan+ and Milan? patients, respectively (p = 0.00001). Both MVI and the Milan criteria were associated with a lower overall and DFS, but only the Milan criteria were associated with the rate of early recurrence and the feasibility of a curative treatment of the recurrence. The application of MVI parameters to patients classified by the Milan criteria further selects the outcome in Milan+ patients (5-year survival rate of 54.1 and 67.9 %, respectively, in the presence or absence of MVI) but not in Milan? patients.

Conclusions

MVI is related to survival after LR for HCC, but the clinical value of this information is limited. In Milan+ patients, the absence of MVI selects the cases with better prognosis. In the presence of a liver recurrence, the Milan criteria related to the primary HCC show a better prognostic accuracy and have clinical relevance in the decision-making process.     

Endoscopic versus Open Radiofrequency Ablation for Treatment of Small Hepatocellular Carcinoma

Background

Surgical radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is associated with superior oncological outcome in comparison with percutaneous RFA. The present study aimed to retrospectively evaluate the relative perioperative safety and postoperative outcome of the laparoscopic or thoracoscopic approach versus the open approach to RFA for small HCC.

Methods

A retrospective analysis was performed in 55 consecutive patients who underwent open (n = 32) or laparoscopic/thoracoscopic (LTS) RFA (n = 23) for primary unresectable HCC between January 2005 and December 2010. Baseline characteristics, survival/recurrence rates, and complications after treatment were compared between the two groups.

Results

There was a trend showing that LTS RFA was performed for tumors located in the anterior segment (e.g., segments III, V, VIII). The LTS RFA group had a significantly lower intraoperative blood loss, shorter operative time, and shorter postoperative hospital stay, compared with the open RFA group. No major postoperative complications occurred in patients who underwent LTS RFA. No significant differences in overall survival, recurrence-free survival and local recurrence rates were observed between the two groups.

Conclusions

In consideration of operative invasiveness and postoperative recovery, LTS RFA is superior to the open approach in patients with small HCC. Moreover, the surgical outcome did not differ between the two approaches. Laparoscopic/thorascopic RFA can be considered to be a useful procedure for ablation therapy.     

Surgical Resection versus Open-Approach Radiofrequency Ablation for Small Hepatocellular Carcinomas within Milan Criteria after Successful Transcatheter Arterial Chemoembolization

Aims

The aim of this study was to compare the effectiveness and safety of hepatic resection versus open-approach RFA (ORFA) for small hepatocellular carcinomas (HCC) within Milan criteria after successful downstaging therapy by transcatheter arterial chemoembolization.

Material and Methods

Between February 2005 and February 2008, a total of 110 patients with advanced HCC met the Milan criteria after successful downstaging therapy; 58 patients then underwent hepatic resection and 52 received ORFA. Outcomes, including short- and long-term morbidity, 1-, 3-, and 5-year mortality and HCC-free survival, were analyzed and compared between the two groups.

Results

Patients in the hepatic resection and ORFA groups showed similar baseline characteristics and downstaging protocols. The ORFA group showed less blood loss, lower hospital costs, shorter surgical time, and fewer hospital stay days (P?<?0.05). The 1-, 3-, and 5-year overall survival rates were 94.8, 86.2, and 79.3 %, respectively, with liver resection and 96.2, 82.7, and 76.9 % with ORFA (P?=?0.772). The 1-, 3-, and 5-year recurrence-free survival rates were 93.1, 81.0, and 77.6 % with resection and 94.2, 76.9, and 73.1 % with ORFA (P?=?0.705). The ORFA patients suffered fewer postoperative complications (P?=?0.09), particularly among the cases of central HCC (P?=?0.015).

Conclusion

Resection and ORFA achieved similar survival benefits in the management of HCC within Milan criteria after successful downstaging. The decreased blood loss, hospital costs, surgical time, and hospital stay days, and lower complication rates in central cases render ORFA a preferred treatment option.     

The Efficacy of Cytokine-Induced Killer Cell Infusion as an Adjuvant Therapy for Postoperative Hepatocellular Carcinoma Patients

Background

Even after surgery, hepatocellular carcinoma (HCC) has poor prognosis; adjuvant therapy is needed to improve effectively the outcome of HCC patients. We evaluated the efficacy of cytokine-induced killer (CIK) cell infusion as an adjuvant therapy for postoperative HCC patients.

Methods

A total of 410 patients were studied retrospectively (January 2002 to January 2007): 206 received surgery alone; 204 received surgery and at least four cycles of CIK cell transfusion (CIK group). Kaplan–Meier and Cox regression analyses were used to explore differences in OS between two groups.

Results

The CIK group overall survival rates were significantly higher than that of the surgery-alone group (log-rank test; p = 0.0007). Multivariate survival analysis showed that CIK cell treatment was an independent prognostic factor. In subgroup analysis, patients who received ≥8 cycles of CIK cell transfusion exhibited significantly better survival than the <8 cycle group (p = 0.0272). There was no significant difference in overall survival in patients with ≤5-cm tumors between the CIK and surgery-alone groups (p = 0.7567). However, in patients with >5-cm tumors, the CIK group displayed significantly better overall survival than the surgery-alone group (p = 0.0002).

Conclusions

Postoperative immunotherapy with CIK cell transfusion may be an effective adjuvant treatment for improving the outcomes of HCC patients; >8 cycles of CIK cell transfusion may ensure that patients derive maximal benefits. Moreover, patients with large tumors might benefit more from CIK cell adjuvant treatment than patients with small tumors.     

Comparison of Surgical Resection and Transarterial Chemoembolization for Hepatocellular Carcinoma beyond the Milan Criteria: A Propensity Score Analysis

Background

Treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) is controversial. This study compared the long-term survival of patients beyond the Milan criteria who received surgical resection (SR) or transarterial chemoembolization (TACE).

Methods

A total of 268 and 455 HCC patients beyond the Milan criteria undergoing SR and TACE, respectively, were retrospectively evaluated. After propensity score analysis to adjust for baseline differences, 146 pairs of matched patients were selected from each treatment arm. Long-term survival was compared by the Kaplan?CMeier method. Independent prognostic predictors were determined by the Cox proportional hazards model.

Results

Long-term survival was significantly better for the SR group by univariate survival analysis (P?P?P?P?Conclusions For HCC patients beyond the Milan criteria, SR is considered equally safe as TACE and provides better long-term survival. SR may be regarded as the priority treatment for these patients.     

Downstaging Advanced Hepatocellular Carcinoma to the Milan Criteria May Provide a Comparable Outcome to Conventional Milan Criteria

Background and Aims

Many hepatocellular carcinoma (HCC) patients met the appropriate criteria and accepted liver transplantation after successful downstaging therapies; however, the outcome in these patients is unclear. We aim to compare the outcome of patients meeting the Milan criteria at the beginning and after successful downstaging therapies.

Patients and Methods

Between July 2001 and January 2013, 112 patients were diagnosed with early-stage HCC that met the Milan criteria. Of these patients, 58 patients did not meet the Milan criteria initially but did after successful downstaging therapies. We retrospectively collected and then compared the baseline characteristics, postoperative complications, survival rate, and tumor recurrence rate of these two groups. Kaplan–Meier analyses were used to estimate the long-term overall survival and tumor-free survival in these patients.

Results

No significant differences were observed between the two groups with respect to baseline donor and recipient characteristics. The downstaging Milan group showed similar tumor characteristics compared to the conventional Milan group, except the downstaging group had better tumor histopathologic grading (P?=?0.027). The 1-, 3-, and 5-year overall survival rates were comparable at 91.4, 82.8, and 70.7 %, respectively, in the downstaging Milan criteria and 92.0, 85.7, and 74.1 %, respectively, according to the initial Milan criteria (P?=?0.540). The 1-, 3-, and 5-year tumor-free survival rates between the two groups were not statistically significant (P?=?0.667).

Conclusion

Successful downstaging therapies can provide a comparable posttransplantation overall survival and tumor-free survival rates after liver transplantation.     

Immediate Radical Therapy or Conservative Treatments When Meeting the Milan Criteria for Advanced HCC Patients After Successful TACE

Background and aims

Many advanced hepatocellular carcinoma (HCC) cases can be successfully downstaged into the Milan criteria; however, immediate radical therapy cannot be applied to all such patients for various reasons. Of the patients who are not eligible for immediate radical therapy, some accept repeated downstaging therapies and some undergo persistent observation. The aim of the present study was to compare long-term survival between these two groups of patients.

Patients and Methods

Between August 2003 and October 2008, 156 HCC patients successfully received downstaging therapy resulting in compliance with the Milan criteria. Of those, 98 cases accepted radical therapies, including liver transplantation (LT), resection, or radiofrequency ablation (RFA) (group 1), and 58 cases underwent repeated transcatheter arterial chemoembolization (TACE) or persistent observation (group 2). The baseline characteristics, demographic data, downstaging protocol, and information on long-term outcomes were collected and compared.

Results

No significant differences were observed in the patient demographic data, downstaging protocols, or tumor characteristics between the two groups. The 1-, 3-, and 5-year overall survival rates were 92.9, 82.7, and 78.6 %, respectively, in group 1, whereas these rates were 82.8, 65.5, and 48.3 %, respectively, in group 2 (P?=?0.046). Among the 58 patients in group 2, the 1-, 3-, and 5-year overall survival rates were 92.3, 65.4, and 46.2 %, respectively, in the repeated TACE group, and 81.3, 65.6, and 50 %, respectively, in the persistent observation group (P?=?0.783).

Conclusion

Immediate radical therapy should be the first choice for advanced HCC patients who undergo successful TACE, and repeated TACE is unnecessary.     

Combination of Morphologic Criteria and α-Fetoprotein in Selection of Patients With Hepatocellular Carcinoma for Liver Transplantation Minimizes the Problem of Posttransplant Tumor Recurrence

Background

Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria.

Methods

This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria.

Results

There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival—significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs.

Conclusions

Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.     

Clinical Analysis of Anatomical Resection for the Treatment of Hepatocellular Carcinoma Based on the Stratification of Liver Function

Background

This study aimed to clarify the efficacy of anatomical resection (AR) for the treatment of hepatocellular carcinoma (HCC) compared with that of nonanatomical resection (NAR) based on the stratification of liver function (LF).

Methods

The clinical records of 174 patients with a single HCC, 2–5 cm in diameter and without macroscopic vascular invasion, were analyzed. AR was performed in 132 patients and NAR was performed in 42 patients. The indocyanine green retention rate at 15 min (ICGR15) of the 78 patients classified as the good-LF group was 10–20 % and the ICGR15 of the 54 patients classified as the poor-LF group was 20–40 %.

Results

The 5-year overall survival (OS) and disease-free survival rates of the 174 patients were 67.6 and 33.4 %, respectively. Cox proportional hazard analysis identified ICGR15 ≥20 %, liver cirrhosis, α-fetoprotein ≥100 mg/dL, and infiltrating growth as independent prognostic factors. Liver cirrhosis was significantly less frequent in patients who underwent AR than in patients who underwent NAR (52 vs. 79 %, p = 0.002). In the subgroup analysis of the good-LF group, there were no significant differences in 5-year OS after AR and NAR (73.3 vs. 65.2 %, p = 0.857). By contrast, in the subgroup analysis of the poor-LF group, the 5-year OS after AR was significantly worse than after NAR (45.3 vs. 77.4 %, p = 0.044).

Conclusion

In patients with an ICGR15 ≥20 %, we recommend NAR rather than AR for the treatment of a solitary 2–5-cm-diameter HCC and without macroscopic vascular invasion.     

Complementary Use of Resection and Radiofrequency Ablation for the Treatment of Colorectal Liver Metastases: An Analysis of 395 Patients

Background

Liver resection and radiofrequency ablation (RFA) are two surgical options in the treatment of patients with colorectal liver metastases (CLM). The aim of this study was to analyze patient characteristics and outcomes after resection and RFA for CLM from a single center.

Methods

Between 2000 and 2010, 395 patients with CLM undergoing RFA (n = 295), liver resection (n = 94) or both (n = 6) were identified from a prospective IRB-approved database. Demographic, clinical and survival data were analyzed using univariate and multivariate analyses.

Results

RFA patients had more comorbidities, number of liver tumors and a higher incidence of extrahepatic disease compared to the Resection patients. The 5-year overall actual survival was 17 % in the RFA, 58 % in the Resection group (p = 0.001). On multivariate analysis, multiple liver tumors, dominant lesion >3 cm, and CEA >10 ng/ml were independent predictors of overall survival. Patients were followed for a median of 20 ± 1 months. Liver and extrahepatic recurrences were seen in 69 %, and 29 % of the patients in the RFA, and 40 %, and 19 % of the patients in the Resection group, respectively.

Conclusions

In this large surgical series, we described the characteristics and oncologic outcomes of patients undergoing resection or RFA for CLM. By having both options available, we were able to surgically treat a large number of patients presenting with different degrees of liver tumor burden and co-morbidities, and also manage liver recurrences in follow-up.     

Single HCC in Cirrhotic Patients: Liver Resection or Liver Transplantation? Long-term Outcome According to an Intention-to-treat Basis

Background

Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis.

Methods

A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1–18) years.

Results

Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18, and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were included on the waiting list for salvage transplantation (very early HCC group) versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p = 0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial survival between the very early HCC group and the LT group (95, 55, and 50 % vs. 82, 62, and 50 %).

Conclusions

LR should be the treatment of choice for cirrhotic patients with very early HCC.